Soybean Oil-Based Lipid Emulsion Increases Intestinal Permeability of Lipopolysaccharide in Caco-2 Cells by Downregulation of P-Glycoprotein via ERK-FOXO 3a Pathway

• Main Authors: Jun-Kai Yan, Jie Zhu, Bei-Lin Gu, Wei-Hui Yan, Yong-Tao Xiao, Ke-Jun Zhou, Jie Wen, Yang Wang, Wei Cai
• Format: Article
• Language: English
• Published: Cell Physiol Biochem Press GmbH & Co KG 2016-09-01
• Series: Cellular Physiology and Biochemistry
• Subjects: Parenteral nutrition; Soybean oil-based lipid emulsion; P-glycoprotein; Lipopolysaccharide; Caco-2
• Online Access: http://www.karger.com/Article/FullText/447860

Background and Aims: Elevated intestinal permeability of lipopolysaccharide (LPS) is a major complication for patients with parenteral nutrition (PN), but the pathogenesis is poorly understood. Intestinal P-glycoprotein (P-gp) is one of the efflux transporters that contribute to restricting the permeability of lipopolysaccharide via transcellular route. P-gp expression may be regulated by PN ingredients, and thus this study sought to investigate the effect of PN on the expression of P-gp and to elucidate the underlying mechanism in vitro. Methods: Caco-2 cells were treated with PN ingredients. Changes in P-gp expression and function were determined and the role of ERK-FOXO 3a pathway was studied. Transport studies of FITC-lipopolysaccharide (FITC-LPS) across Caco-2 cell monolayers were also performed. Results: Among PN ingredients, soybean oil-based lipid emulsion (SOLE) exhibited significant inhibitory effect on P-gp expression and function. This regulation was mediated via activation of ERK pathway with subsequent nuclear exclusion of FOXO 3a. Importantly, P-gp participated in antagonizing the permeation of FITC-LPS (apical to basolateral) across Caco-2 cell monolayers. SOLE significantly increased the permeability of FITC-LPS (apical to basolateral), which was associated with impaired P-gp function. Conclusions: The expression and function of intestinal P-gp is suppressed by SOLE in vitro.